Biomedical subjects

G S Pope

Publications and source records attributed to G S Pope.

At least 19 recordsLinked to original sources

PubMed2005

Comparative study of oestrogenic properties of eight phytoestrogens in MCF7 human breast cancer cells.

Previous studies have compared the oestrogenic properties of phytoestrogens in a wide variety of disparate assays. Since not all phytoestrogens have been tested in each assay, this makes inter-study comparisons and ranking oestrogenic potency difficult. In this report, we have compared the oestrogen agonist and antagonist activity of eight phytoestrogens (genistein, daidzein, equol, miroestrol, deoxymiroestrol, 8-prenylnaringenin, coumestrol and resveratrol) in a range of assays all based within the same receptor and cellular context of the MCF7 human breast cancer cell line. The relative binding of each phytoestrogen to oestrogen receptor (ER) of MCF7 cytosol was calculated from the molar excess needed for 50% inhibition of 3H]oestradiol binding (IC50), and was in the order coumestrol (35x)/8-prenylnaringenin (45x)/deoxymiroestrol (50x)>miroestrol (260x)>genistein (1000x)>equol (4000x)>daidzein (not achieved: 40% inhibition at 10(4)-fold molar excess)>resveratrol (not achieved: 10% inhibition at 10(5)-fold molar excess). For cell-based assays, the rank order of potency (estimated in terms of the concentration needed to achieve a response equivalent to 50% of that found with 17beta-oestradiol (IC50)) remained very similar for all the assays whether measuring ligand ability to induce a stably transfected oestrogen-responsive ERE-CAT reporter gene, cell growth in terms of proliferation rate after 7 days or cell growth in terms of saturation density after 14 days. The IC50 values for these three assays in order were for 17beta-oestradiol (1 x 10(-11)M, 1 x 10(-11)M, 2 x 10(-11)M), and in rank order of potency for the phytoestrogens, deoxymiroestrol (1 x 10(-10)M, 3 x 10(-11)M, 2 x 10(-11)M)>miroestrol (3 x 10(-10)M, 2 x 10(-10)M, 8 x 10(-11)M)>8-prenylnaringenin (1 x 10(-9)M, 3 x 10(-10)M, 3 x 10(-10)M)>coumestrol (3 x 10(-8)M, 2 x 10(-8)M, 3 x 10(-8)M)>genistein (4 x 10(-8)M, 2 x 10(-8)M, 1 x 10(-8)M)/equol (1 x 10(-7)M, 3 x 10(-8)M, 2 x 10(-8)M)>daidzein (3 x 10(-7)M, 2 x 10(-7)M, 4 x 10(-8)M)>resveratrol (4 x 10(-6)M, not achieved, not achieved). Despite using the same receptor context of the MCF7 cells, this rank order differed from that determined from receptor binding. The most marked difference was for coumestrol and 8-prenylnaringenin which both displayed a relatively potent ability to displace [3H]oestradiol from cytosolic ER compared with their much lower activity in the cell-based assays. Albeit at varying concentrations, seven of the eight phytoestrogens (all except resveratrol) gave similar maximal responses to that given by 17beta-oestradiol in cell-based assays which makes them full oestrogen agonists. We found no evidence for any oestrogen antagonist action of any of these phytoestrogens at concentrations of up to 10(-6)M on either reporter gene induction or on stimulation of cell growth.

Biological Assay↗

PubMed2002

Oestrogenic activity of parabens in MCF7 human breast cancer cells.

Parabens (4-hydroxybenzoic acid esters) have been recently reported to have oestrogenic activity in yeast cells and animal models. Since the human population is exposed to parabens through their widespread use as preservatives in foods, pharmaceuticals and cosmetics, we have investigated here whether oestrogenic activity of these compounds can also be detected in oestrogen-sensitive human cells. We report on the oestrogenic effects of four parabens (methylparaben, ethylparaben, n-propylparaben, n-butylparaben) in oestrogen-dependent MCF7 human breast cancer cells. Competitive inhibition of [3H]oestradiol binding to MCF7 cell oestrogen receptors could be detected at 1,000,000-fold molar excess of n-butylparaben (86%), n-propylparaben (77%), ethyl-paraben (54%) and methylparaben (21%). At concentrations of 10(-6)M and above, parabens were are able to increase expression of both transfected (ERE-CAT reporter gene) and endogenous (pS2) oestrogen-regulated genes in these cells. They could also increase proliferation of the cells in monolayer culture, which could be inhibited by the antiestrogen ICI 182,780, indicating that the effects were mediated through the oestrogen receptor. However, no antagonist activity of parabens could be detected on regulation of cell proliferation by 17 beta-oestradiol at 10(-10)M. Molecular modelling has indicated the mode by which paraben molecules can bind into the ligand binding pocket of the crystal structure of the ligand binding domain (LBD) of the oestrogen receptor alpha (ERalpha) in place of 17beta-oestradiol; it has furthermore shown that two paraben molecules can bind simultaneously in a mode in which their phenolic hydroxyl groups bind similarly to those of the meso-hexoestrol molecule. Future work will need to address the extent to which parabens can accumulate in hormonally sensitive tissues and also the extent to which their weak oestrogenic activity can add to the more general environmental oestrogen problem.

Animals↗

PubMed1998

Relationships of peri-partum, plasma concentrations of progesterone, oestrogens and 13,14-dihydro-15-ketoprostaglandin F2alpha in heifers and of anatomical measurements of dam and calf with difficulty of calving in early-bred Hereford x Friesian heifers.

Plasma concentrations of progesterone, oestradiol-17beta, oestrone, oestrone sulphate and PGFM have been measured daily during the first peri-partum period of 45 Hereford x Friesian heifers bred at 11 months of age. Anatomical measurements of dam and calf were also recorded. Twelve of the calvings were scored easy, 33 difficult. Each of five models (fitted by linear logistic regression) relating difficulty of calving to the hormonal and anatomical measurements, predicts with at least 94% accuracy the calving score (easy or difficult) among the calvings. The models predict that increases of progesterone concentration on the day before calving, of oestrone sulphate concentration on the day after calving and of heifer heart girth decrease the odds of difficult calving, whereas increases of heifer body length and of calf head circumference increase the odds of difficult calving.

Animal Feed↗

PubMed1996

Possible roles for prolactin, thyroxine and insulin in the growth of heifers before and during early pregnancy.

Two groups of British Friesian heifers with cyclic ovarian function and the potential for further growth were individually fed a restricted diet at two levels over a 12-week period. Eight heifers receiving the higher level of feed (SP group) and five receiving the lower level (LP group) became pregnant by artificial insemination at week 6. Mean (and SEM) body weight changes in the SP and LP groups were respectively 0.24 (+/- 0.024) kg day-1 and -0.19 (+/- 0.039) kg day-1. Over the period from weeks 3-12, mean concentrations of plasma prolactin, thyroxine and insulin in the five LP heifers were 39%, 67% and 74%, respectively, of those in the eight SP heifers. The results suggest that prolactin, thyroxine and insulin have roles in the growth of heifers before and during early pregnancy.

Animals↗

PubMed1985

Seasonal changes in the testes and accessory reproductive organs and seasonal and circadian changes in plasma testosterone concentrations in the male grey squirrel (Sciurus carolinensis).

A 27-month study of cycles of regression and recrudescence of testis function in adult, grey squirrels in a natural environment in southern England has shown concomitant variation in mean testes weights, mean plasma testosterone concentrations, and mean weights of accessory sex organs, this variation being closely associated with months of the year. Testis regression occurred in the period June to August, the exact timing differing among individuals. In 1979-1980 the testes of all squirrels then remained regressed for 7 months, whereas in the autumn of 1980 testes were regressed in most squirrels for 4 months. There was also evidence of testis regression in some individuals in March 1979 and March 1981. Males born and housed in a small woodland enclosure in 1979-1980 and well fed with grain did not experience the long period of regressed testes. Plasma testosterone concentrations measured hourly over 24 hr in squirrels with large, active testes varied from 0.4 to 20 nmol/l, both within and between individuals, the higher concentrations being observed between midday and midnight. The range in the age of males at puberty, based on fusion of the epiphyses of the wrist, was 1.0 to 1.25 year. Juvenile males housed in a woodland enclosure together with adult males and females remained prepubertal up to 2 years of age.

Animals↗

PubMed1984

Testosterone, 17 beta-hydroxy-5 alpha-androstan-3-one and 4-androstene-3, 17-dione in the plasma of male and female grey squirrels (Sciurus carolinensis).

Extracts of squirrel plasma have been chromatographed on partition columns (using a hydrophilic stationary phase) at atmospheric pressure (Celite support) and a reversed phase system at high pressure (HPLC). Both methods effectively separated testosterone, 17 beta-hydroxy-5 alpha-androstan-3-one (DHT) and 4-androstene-3,17-dione; they gave elution patterns that differed considerably. Chromatographic mobility of the three androgens on the two systems was identical with that of fractions of squirrel plasma extracts that gave responses measured by appropriate androgen radioimmunoassays; good evidence for the occurrence of these androgens in squirrel plasma is thus provided. Plasma testosterone levels were 300 pmol/l in juvenile males, 800-7000 pmol/l in sexually-active males but undetectable (less than 50 pmol/l) in sexually-regressed males. Plasma DHT levels were also high in sexually-active males, but undetectable in other males except for one regressed individual. Plasma androstenedione was higher in juvenile males than in adult males, in which it was similar whether or not they were sexually regressed. Plasma testosterone and DHT, unlike androstenedione, were totally dependent on the presence of the testes. In females testosterone and DHT were undetectable in plasma but androstenedione levels were high, especially at oestrus. Androstenedione was dependent on the presence of the ovaries.

Androstenedione↗

PubMed1983

Fertility of dairy cattle following oestrus and ovulation controlled with cloprostenol, oestradiol benzoate and progesterone or progesterone and cloprostenol.

There have been several approaches to the control of the timing of the oestrous cycle and ovulation in dairy cattle in the last three decades. The first phase involved the use of progestins which were administered in various forms for prolonged periods. Although the timing of oestrus was controlled in most animals after withdrawal of the treatment, this control was not very precise and pregnancy rates from insemination at the first oestrus after treatment were reported to be below normal. Attempts were then made to combine short-term progestin treatments with oestrogens as luteolytic agents to gain better control of the timing of oestrus and ovulation. These studies resulted in some cases in better synchronization of oestrus and improved pregnancy rates. The discovery that prostaglandin F2 alpha (PGF2 alpha) and its synthetic analogue, cloprostenol were potent luetolytic agents in the cow led in the past decade to the use of these agents for oestrus and ovulation control in cattle. Prostaglandins for this purpose are ineffective in anovulatory cows, in cows with deficient luteal function and in the first 5 days of the oestrus cycle when a new corpus luteum is being formed. This limitation in their use has encouraged investigations into the combined use of short-term progestin treatment with prostaglandins to give more effective control of the timing of oestrus and ovulation and to avoid the adverse effects on fertility of long-term progestin treatment. Short-term progestin treatment combined with prostaglandins should mean that fewer cows would have ovulation suppressed for long periods and fertility of treated cows should be improved. A comparison of three procedures of ovulation control and fertility results shows the short-term progestin treatment combined with prostaglandin to be the most effective.

Animals↗

PubMed1983

Oestrogens in milk.

The steroid oestrogens oestradiol-17 beta, oestrone and oestradiol-17 alpha have all been adequately identified in various body fluids and tissues of cattle. There is also good evidence for the presence of oestrone sulphate. Oestriol (or similar triols) may also be present. The oestrogens found in the systemic plasma of cattle are present in milk in similar concentrations; whether their passage into milk involves metabolism by the mammary gland is uncertain. Oestrone sulphate, at least at relatively high levels of secretion, is believed to be found only in pregnant cattle and measurement of its concentration in milk is in use as a practical test for pregnancy. A close correlation has been found between the concentrations of oestradiol-17 beta in systemic plasma and milk of non-pregnant cows and levels of this oestrogen in milk may, together with those of progesterone, now be used in studies of post-partum ovarian function.

Animals↗

PubMed1981

Progesterone concentrations in peripheral plasma of non-pregnant and pregnant grey squirrels (Sciurus carolinensis).

Plasma concentrations of progesterone in non-pregnant female grey squirrels were never greater than 3.2 nmol/l and no significant differences were found between levels in anoestrous, pro-oestrous and oestrous animals. During pregnancy, plasma concentrations of progesterone increased significantly and reached a maximum level of 318 nmol/l at around day 35 of the 44 day period of gestation. After parturition, plasma concentrations of progesterone fell sharply. The corpora lutea of pregnancy began to regress in size at about day 30 of gestation, before the maximum levels of progesterone in the plasma were reached, which suggests that there is an extra-ovarian source of progesterone. Chromatography of pregnancy plasma extracts showed that no significant amount of 5 alpha- or 5 beta-pregnane-3,20-dione was present and that progesterone accounted for 90% of the assay-positive material in pregnancy plasma from grey squirrels.

Animals↗

PubMed1981